Unless they receive antimycobacterial prophylaxis in some form, up to 40 percent of patients have disseminated Mycobacterium avium complex infection within two years of the diagnosis of the. Mycobacterium avium complex (MAC) causes disseminated disease in up to 40% of patients with human immunodeficiency virus (HIV) in the United States, producing fever, sweats, weight loss, and anemia (1-3). Disseminated MAC characteristically affects patients with advanced HIV disease and peripheral CD4+ T-lymphocyte counts less than 100 cells/uL. The 2 most common causes of NTM PD in Ontario, Canada, are Mycobacterium avium complex (MAC) and M. MAC assembly is controlled in two ways—by proteins that bind to the C5b-7 complex and by proteins that inhibit C9 incorporation and polymerization within the MAC. Nascent C5b-7 molecules have the potential to insert into any cell membrane and are not restricted to the surface on which complement is activated.
Mycobacterium avium complex (MAC) refers to infections caused by two types of bacteria: Mycobacteriumavium and Mycobacteriumintracellulare.[1][2] MAC bacteria do not make most people sick. However, people with immune systems that do not work well (from HIV/AIDS or certain cancers for example) or people with lung disease (such as chronic obstructive pulmonary disease (COPD) or cystic fibrosis) are at the greatest risk for getting sick from MAC Infections. Elderly women are also at higher risk to get sick from MAC infections.[2][3] There are 3 types of MAC infections.
Pulmonary MAC infections - Affect the lungs and are the most common type. These mainly affect elderly women and people who already have lung disease.[2][3]
Disseminated MAC infections - Have spread throughout the body. This type is usually seen in people with advanced AIDS.[1]
MAC-associated lymphadenitis - Causes swelling of the lymph nodes (especially in the neck) and is the most common in young children who have normal immune systems.[3][4]
While the symptoms are different for each type of infection, general symptoms include fever, night sweats, weight loss, and fatigue. MAC bacteria are found in water, soil, and dust. They infect people when the bacteria are inhaled or swallowed.[1][5] MAC bacteria are not usually spread from person to person. MAC infections are diagnosed by a combination of imaging scans and identifying the bacteria in cultures of cells from the infected area. Treatment for MAC infection depends on the type and may include antibiotics, antiviral medications, or surgery.[1][2]
Last updated: 11/8/2018
Mycobacterium avium complex infections can cause various symptoms depending on the site of the infection. For example, pulmonary MAC mainly affects the lungs; disseminated MAC affects the whole body; and MAC lymphadenitis causes swollen lymph nodes.[1][2][4]
The symptoms of pulmonary MAC infection start slowly, get worse over time and may last for weeks to months. People with pulmonary MAC infections may experience cough, weight loss, fever, fatigue, and night sweats.[2] Symptoms of disseminated MAC infection include: [1][4]
Fever
Sweating
Weight loss
Fatigue
Diarrhea
Shortness of breath
Abdominal pain
Anemia
People with disseminated MAC infection may also have symptoms associated with an infection of the breast tissue (mastitis); an infection of the skeletal muscle (pyomyositis), abscesses of the skin or brain, and gastrointestinal problems.[1][3] MAC lymphadenitis generally affects children with normal immune systems. Symptoms of MAC lymphadenitis usually only include swollen lymph nodes mainly on one side of the neck.[1][3]
Mycobacterium avium complex (MAC) infections are caused by two types of bacteria: Mycobacterium avium and Mycobacterium intracellulare.[1] These bacteria are found in many places including water (fresh or salt), household dust, and soil. MAC bacteria get into the body when the bacteria are inhaled into the lungs or swallowed. Most people have MAC bacteria in their bodies and never get sick. MAC bacteria primarily cause illness in people who have poorly working immune systems or lung disease. Touching the same objects or having a close relationship with people who are sick from a MAC infection does not seem to increase the chance of getting sick. MAC infections are not thought to be contagious from one person to another.[3][4]
Mycobacterium avium complex (MAC) infection is caused by bacteria and is not an inherited condition. To become infected with MAC bacteria and get sick, a person must first be exposed to one of the associated types of bacteria.[4] There have been a few reports of families with more than one family member with a MAC infection. In these families, it is thought that there is a variation in a gene or genes involved with the body's immune response. A genetic variant in an immune system gene may make some people more likely to get sick from an infection than others. There are many genes involved in the human immune response, and there is no single gene known to be responsible for MAC infections.[3][4]
Diagnosis of a pulmonary mycobacterium avium complex (MAC) infection is based on a combination of physical exam findings, laboratory test results, and lung x-rays or CT scan results. The laboratory tests include cultures of mucus spit up from the lungs (sputum) and special staining (acid-fast bacillus test). A laboratory culture involves placing cells from a sputum sample in an environment that encourages the bacteria to grow. Results identifying the bacteria may take several days or longer. Because the symptoms of MAC infections are similar to those of other types of infections, other types of infections and diseases must also be ruled out.[3][4] Diagnosis of disseminated MAC infection is suspected based on symptoms and is confirmed in cultures of blood and often lymph node cells. Cultures of cells from urine, stool, liver or bone marrow may also be helpful. CT scans may be used to try to determine the different sites of infection in the body. If pulmonary or disseminated MAC infection is suspected, an HIV test may be done, as well as other tests, to rule out other associated medical conditions.[1][2][3] A diagnosis of MAC lymphadenitis is confirmed by finding the bacteria in the culture of lymph node cells. These cells are collected by a biopsy of a swollen lymph node.[2][3]
Mycobacterium avium complex (MAC) infection is classified into several different types including:[2][3]
Pulmonary MAC infection, which affects the lungs
Disseminated MAC infection, which affects many different parts of the body
MAC lymphadenitis, which causes swollen lymph nodes
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Treatment options for MAC infections vary by type of infection and by the presence of other medical conditions such as AIDS, cystic fibrosis, COPD, or cancer.[3]
Pulmonary MAC infections and disseminated MAC infections are usually treated with a combination of antibiotic medications. There are many types of antibiotics approved for treating MAC infections A combination of medicines is used because some of the disease-causing bacteria can be resistant to certain types of antibiotics. Using more than one antibiotic reduces the chance for the MAC bacteria to come back after treatment is over.[1][3] For people who have both HIV/AIDS and a MAC infection, treatment usually involves a combination of different antibiotics for the MAC infection and antiretroviral therapy to treat the HIV infection.[1][4] In special circumstances, there is some evidence to suggest that surgery to remove a single spot of infection in one lung can be helpful in people who have had a poor response to drug therapy. Surgery is usually only done when the infection is found in only one lung and the surgery won't cause any long-term harm.[3][4] Treatment of MAC lymphadenitis usually involves surgical removal of affected lymph nodes. Antibiotics may also be prescribed depending on the severity of infection and the response to surgery.[3][4]
FDA-Approved Treatments
The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.
Liposomal amikacin(Brand name: Arikayce) - Manufactured by Insmed Incorporated FDA-approved indication: September 2018, liposomal amikacin (Arikayce) was approved for the treatment of Mycobacterium avium complex (MAC) lung disease as part of a combination antibacterial drug regimen in patients who do not achieve negative sputum cultures after a minimum of 6 consecutive months of a multidrug background regimen therapy. National Library of Medicine Drug Information Portal Medline Plus Health Information
The long-term outlook (prognosis) for people who are sick from mycobacterium avium complex (MAC) infections depends on the type of infection and whether or not the person has other medical conditions or health problems. One published study reviewed the long-term outlook of people with MAC infections with and without other diseases, and found a 75% chance for survival five years after their first diagnosis.[6] People who are HIV-positive with MAC infections may have a shortened lifespan depending on their immune systems and their response to HIV medications. For people who have had successful treatment, there is still a chance that the infection will come back, so people who have been sick from a MAC infection need to be monitored over time.[2][3] In HIV-negative people with lung disease from a MAC infection, the treatment success rates range from 20-90% in different studies.[2] People with certain types of lung disease, people who are underweight, and people with anemia are more likely to have a poor outcome than other HIV-negative people affected by a MAC infection. MAC lymphadenitis in children generally does not impact their health. In some cases, the condition may go away even without treatment.[3]
Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.
Clinical Research Resources
ClinicalTrials.gov lists trials that are related to Mycobacterium Avium Complex infections. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies. Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.
Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.
Organizations Supporting this Disease
NTM Info & Research (supports pulmonary NTM infections) 550 Madruga Avenue, Suite 230 Coral Gables, FL 33146 Telephone: 305-667-6461, ext 26 and 32 E-mail: [email protected] Website: http://www.ntminfo.org/
These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.
Where to Start
The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.
In-Depth Information
Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
PubMed is a searchable database of medical literature and lists journal articles that discuss Mycobacterium Avium Complex infections. Click on the link to view a sample search on this topic.
The AIDS Education and Training Center (AETC) offers information on Mycobacterium Avium Complex infections. Click on the link to view this information page.
News
NIH-Supported Research Survey to Examine Impact of COVID-19 on Rare Diseases Community May 22, 2020
Questions sent to GARD may be posted here if the information could be helpful to others. We remove all identifying information when posting a question to protect your privacy. If you do not want your question posted, please let us know.
Griffith DE. Overview of nontuberculous mycobacterial infections in HIV-negative patients. UpToDate. 2017; https://www.uptodate.com/contents/overview-of-nontuberculous-mycobacterial-infections-in-hiv-negative-patients.
Koirala J. Mycobacterium Avium-Intracellulare. Medscape Reference. 2018; http://emedicine.medscape.com/article/222664-overview.
Disseminated mycobacterium avium complex disease. US Department of Health and Human Services. 2017; https://aidsinfo.nih.gov/guidelines/html/4/adult-and-adolescent-opportunistic-infection/326/mac.
Diel R, Lipman M, Hoefsloot W. High mortality in patients with Mycobacterium avium complex lung disease: a systematic review. BMC Infect Dis. 2018; 18(206):1-10. https://bmcinfectdis.biomedcentral.com/track/pdf/10.1186/s12879-018-3113-x.
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WHAT IS MAC (MYCOBACTERIUM AVIUM COMPLEX) AND HOW IS IT DIAGNOSED AND TREATED?
Formerly known as “atypical mycobacteria”, “atypical TB”, or “atypical AFB” and currently as “nontuberculous mycobacteria” or “NTM”. NTM includes all types or species of mycobacteria (including MAC) other than the germ of tuberculosis (TB).
Related to Mycobacterium tuberculosis (Mtb) but it is not TB (tuberculosis).
NTM includes a number of different species, but the most common one causing chronic lung disease is MAC.
MAC is not spread person to person like Mtb. MAC is not contagious.
MAC lung disease seen in HIV negative (non-AIDS) patients is a chronic lung infection and early-on is often misdiagnosed as chronic bronchitis or recurrent pneumonia.
MAC Lung Disease is acquired from the environment (soil, air, natural waters, tap water, etc.)
Scientists and physicians who have studied MAC believe people who develop MAC lung disease become infected because of a defect in the structure or function of their lungs (especially a disease called bronchiectasis) or in their immune systems.
Damaged lung tissue can result from previous TB, heavy smoking, and a breathing tube disease called bronchiectasis.
Bronchiectasis is a breathing tube (bronchial) disorder characterized by excessive mucus production, cough, and susceptibility to certain infections such as MAC or infection caused by bacteria such as Pseudomonas aeruginosa.
Disease in men commonly relates to smoking while disease in women (non-smoking) usually relates to bronchiectasis.
The average age of patients with MAC lung disease in men is 55 years and 67 years in women.
Men are more likely to have cavitary MAC (holes in their lungs). Women are more likely to have non-cavitary, nodular MAC.
Diagnosis of MAC lung disease usually requires:
Medical history with records of symptoms:
Cough, sputum production, shortness of breath
Loss of appetite (anorexia is the medical term) weight loss
Severe fatigue or tiredness with inability to perform daily tasks
Rarely coughing up blood (hemoptysis is the medical term)
Fever, night sweats
Chest x-ray (a picture of your lungs internally)
High resolution CT scan (HRCT) (similar to an x-ray but a more detailed picture)
Sputum culture – several sputum cultures are usually performed. Your specimen coughed from your lungs is examined under a microscope (AFB smear) and also placed on special media to grow mycobacteria (AFB culture).
Bronchoscopy – may be necessary in some cases (especially if you can not cough up sputum) but not all, and involves putting a tube down into your lungs to obtain specimens for culture.
TREATMENT OF MAC LUNG DISEASE REQUIRES A MULTI-DRUG REGIMEN (MORE THAN ONE DRUG).
MAC is resistant to ordinary antibiotics.
Combination of 3 drugs (all FDA approved)/dosages are based upon your clinical history, age, weight, and symptoms.
Clarithromycin (Biaxin) or Azithromycin (Zithromax)
Rifampin (Rifadin) or Rifabutin (Mycobutin)
Ethambutol (Myambutol)
The combination of medicines is given until no more MAC germs can be grown by culture of your sputum for 1 year. Average treatment period is about 15-18 months.
Monthly sputum cultures are performed while you are on therapy and periodically when you finish your therapy to be sure your MAC is gone.
The 3-drug treatment may be given 3 times weekly (preferably Monday-Wednesday-Friday) or daily.
Data from previous treatment trials tells us that most patients (approximately two-thirds) who have no previous treatment of their MAC and who can tolerate the appropriate medicines will get better and be “cured” of their MAC lung disease.
Patients who have failed a prior drug regimen of > 6 months for their MAC are more likely to fail the standard drug regimen (almost 50%).
Patients who take the 3-drug regimen for less than 1 year with negative cultures are more likely to relapse with disease with their same MAC strain.
Patients who fail therapy after taking the 3 medicines are usually required to take additional medicines. Injectables which may be useful include:
Streptomycin or Amikacin
Amikacin can also be given by inhalation (aerosolized) and is less toxic when given in this manner.
Monthly laboratory blood tests that include a complete blood count and comprehensive metabolic panel (CBC and CMP) to check for possible damage to blood cells, kidneys, and liver.
Most common potential side effects/complications of medicines:
Clarithromycin : Loss of appetite, diarrhea, nausea, abdominal pain, abnormal liver function tests (blood tests), bitter taste, mild allergic rash.
Azithromycin : Diarrhea, nausea, abdominal pain, abnormal liver function tests (blood tests), decreased hearing, tinnitus (sounds in ears).
Rifampin : Nausea, vomiting, liver damage, decreased platelets (cells which clot blood), body secretions (urine primarily) are orange/red.
Rifabutin : Nausea, vomiting, decreased platelets, decreased white blood cells (cells that fight infection), eye pain (uveitis), diffuse muscle and joint aches, skin pigmentation (yellow).
Ethambutol : Decrease in vision (especially color vision), blurriness.
Amikacin : Kidney damage, tinnitus, hearing loss, poor balance. If you experience these or other additional problems, you should discuss them with your physician.
Amikacin by inhalation (aerosolization) decreases toxicity to above adverse events.
Provide a list of your current medicines to your physician so he can determine any possible contra-indications.
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PULMONARY FUNCTION TESTING
What is a pulmonary function test?
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Pulmonary function testing is a way to measure your breathing capacity and, therefore is an objective measure of how well you are breathing. There are several types of breathing tests that can be done during pulmonary function testing including spirometry, lung volumes and diffusing capacity. A technician will explain what you need to do during each test and will coach you during the tests to help you give a good effort. All breathing tests require more than one measurement so that you will be asked to make more than one effort for each test. Spirometry is the most commonly performed breathing test. It requires you to take in as deep a breath as possible and then blow out the air in your lungs as forcefully and fully as possible. Spirometry, therefore, measures how much air you breathe in and out and how fast you breathe air in and out. Spirometry is frequently performed at baseline and then after you have inhaled a bronchial dilating drug (breathing medicine) to evaluate the effect of medication on your breathing function. As with all pulmonary function tests, it is very important that you make a maximal effort to insure accurate assessment of your breathing function. Lung volumes are performed while you are sitting in a small chamber called a plethysmograph (or body box) and provide further information about how much air you breathe in and out. You will be asked to perform different breathing techniques such as blowing into a tube while in the chamber. Lung volumes are usually not performed unless there are abnormalities found on spirometry. The diffusing capacity is one measure of how well your lungs move oxygen from the lungs into the blood. The results of pulmonary function testing can tell you and your doctor how much your lungs have been affected by a disease process and help determine if specific therapy can be of benefit to you. They can also be useful for evaluating the effects of a disease or treatment over time. You will be given specific instructions about what to do with your own breathing medications when the breathing tests are scheduled. Pulmonary function testing usually takes between ½ to 1 ½ hour to complete, depending on how many of the pulmonary function tests you are asked to complete.
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Also see the http://www.uthct.edu website for further information including on how to arrange a clinic visit for expert consultation on MAC. Other centers that can also provide such consultation are found under the List of Treating Institutions.